1. Field of the Invention
The invention relates to a biosensor, and in particular to a biosensor comprising a ruthenium nitride or ruthenium oxide film and the application thereof.
2. Description of the Related Art
The Ion Sensitive Field Effect Transistor (ISFET), first proposed by Piet Bergveld in 1970, is similar to the conventional MOSFET (Metal-Oxide-Semiconductor Field Effect Transistor) except that a sensitive film is used in place of the metal gate of the MOSFET. The extended gate ion sensitive field effect transistor (EGISFET) developed from ISFET combines the extended gate containing a sensing membrane with the MOSFET by a conducting wire and has the advantages of simple structure, easy package procedure, low cost, and flexibility in biomedical application. In addition, EGISFET can be prepared with the CMOS standard process and the obtained EGISFET has higher sensitivity in detecting pH value of a solution. However, the sensing membranes presently in use, including IrO2 and SnO2, are not materials for the CMOS standard process.
Patents related to the manufacture of ISFET include U.S. Pat. Nos. 6,409,909 and 6,326,215. U.S. Pat. No. 6,409,909 discloses a modular, in particular multidimensional system for the reagent-free continuous detection of a substance. This system is characterized by the presence of at least two measuring modules of preferably different types. The modules are robust and designed for a long-time operation. An exchangeable or replaceable selective layer structure is included. The system may also include appropriate modules for amperometry and optical sensors. U.S. Pat. No. 6,326,215 discloses a sensor for sensing the presence of an analyte without relying on redox mediators. This sensor includes (a) a plurality of conductive polymer strands each having at least a first end and a second end each aligned in a substantially common orientation; (b) a plurality of molecular recognition headgroups having an affinity for the analyte and being attached to the first ends of the conductive polymer strands; and (c) an electrode substrate attached to the conductive polymer strands at the second ends. The electrode substrate is capable of reporting to an electronic circuit reception of mobile charge carriers (electrons or holes) from the conductive polymer strands. The electrode substrate may be a photovoltaic diode. Also disclosed is a method of forming a sensor capable of sensing the presence of an analyte component. This method includes (a) contacting a sensor substrate (e.g., a device element of a device on semiconductor chip) with a first medium containing mobile conductive polymer strands or precursors of the conductive polymer strands; (b) applying a first potential to the substrate sufficient to form a first structure having the conductive polymer strands affixed into the substrate; (c) contacting the sensor substrate, with affixed conductive polymer strands, with a second medium containing mobile molecular recognition headgroups; and (d) applying a second potential to the substrate sufficient to affix the molecular recognition headgroups to the affixed conductive polymer strands.
U.S. Pat. No. 6,218,208 to the inventors discloses a sensitive material-tin oxide (SnO2) obtained by thermal evaporation or by RF reactive sputtering used as a high-pH-sensitive material for a Multi-Structure Ion Sensitive Field Effect Transistor (ISFET). The multi-structure ISFET has high performances such as a linear pH sensitivity of approximately 56-58 mV/pH in a concentration between pH 2 and pH 10. A low drift characteristic of approximately 5 mV/day, response time of less than 0.1 second, and an isothermal point of this ISFET sensor can be obtained if the device operates with an adequate drain-source current. In addition, this ISFET sensor has other advantages, such as inexpensive fabrication, low cost, and mass production characteristics.
In addition, U.S. Pat. No. 5,911,873 discloses an apparatus for measuring ion concentration of a solution, comprising an ion sensitive field effect transistor (ISFET), a reference device, an ISFET control circuit, a memory, a measurement circuit and a diagnostic circuit. The ISFET has a drain, a source, an ion sensitive gate region and a plurality of device characteristics. The reference device is separated from the gate region by a sample solution. The ISFET control circuit is coupled to the ISFET and operates the ISFET at a drain-source voltage VDS and at n successive drain currents IDi and corresponding gate-source voltages VGSi, wherein I is an integer from 1 to n and n is an integer greater than 1. The memory stores the plurality of device characteristics and the n successive drain currents IDi and gate-source voltages VGSi. The measurement circuit measures ion concentration of the solution as a function of at least one of the n successive drain currents IDi and gate-source voltages VGSi and the plurality of device characteristics stored in the memory. The diagnostic circuit measures at least one of the device characteristics of the ISFET as a function of the n successive drain currents IDi and gate-source voltages VGSi. U.S. Pat. No. 5,384,028 discloses a biosensor, provided with a memory for storing data including data and time of fabrication of the biosensor, lot number of the biosensor, effective period of the biosensor, biosensor characteristics, and administrative data of the biosensor. The memory may store additional data such as the measured data, the consecutive (total) measuring time, the measured results, etc. U.S. Pat. No. 5,309,085 discloses a measuring circuit with a biosensor utilizing ion sensitive field effect transistors having a simplified structure, advantageous to integration. The measuring circuit comprises two ion sensitive FET input devices composed of an enzyme FET having an enzyme sensitive membrane on the gate and a reference FET, and a differential amplifier for amplifying the outputs of the enzyme FET and the reference FET. The drift phenomena of the ISFETs from use of a non-stable quasi-reference electrode as well as the temperature dependence thereof can be eliminated by the differential amplifier consisting of MOSFETs having the same channel as the ISFETs. The ISFET biosensor and the measuring circuit can be integrated into one chip.
Conventional electrochemical systems having three electrodes employ (1) a working electrode, (2) a reference electrode, and (3) a counter electrode. The reaction at the working electrode is monitored and controlled. The functions of the reference and counter electrodes ensure that the working electrode actually experiences the desired conditions, i.e. the correct potential to be applied. The reference electrode measures the potential at the interface of the working electrode and the sample as accurately as possible. In an ideal situation, no current passes through the reference electrode. The counter electrode ensures that the correct potential difference between the reference electrode and the working electrode is being applied. The potential difference between the working electrode and the reference electrode is assumed to be the same as the desired potential at the working electrode. If the potential measured at the working electrode is not the potential desired at the working electrode, the potential applied between the counter electrode and working electrode is altered accordingly, i.e., the potential is either increased or decreased. The reaction at the counter electrode is also equal and opposite to the charge transfer reaction occurring at the working electrode, i.e., if an oxidation reaction is occurring at the working electrode then a reduction reaction will take place at the counter electrode, thereby allowing the sample to remain electrically neutral.
In the ISFET applications, however, many factors such as hysteresis, temperature, and drift behavior affect the accuracy of the measuring results. The variation of the temperature leads to a deviation in measurement due to ion sorption of a sensing membrane differing at various temperatures. With reference to the hysteresis behavior, it is related to the change in the pH of the solution (such as pHx→pHy→pHx→pHz→pHx) and the corresponding change in the output voltage of the ISFET (such as Vox1→Voy→Vox2→Voz→Vox3). At the same pH, the difference between the first output voltage and the final output voltage (such as Vox3→Vox1) is defined as the hysteresis width. For drift behavior, the drift rate is defined as the change in the gate voltage per unit time under conditions in which the source-drain current is stable and the temperature is constant after the intrinsic response of the pH-ISFET is completed. Hence, there is a need to measure the three effects to prevent error.
Various materials are used as the sensing membrane of ISFET and EGISFET, such as Al2O3, Ta2O5, Si3N4, SnO2, and the like. These materials can be prepared by sputtering or plasma chemical vapor deposition, however, they still have some drawbacks in practice. A sensing film with low cost and simple process is, however, still required for commercial application.